lead-in folicolor trial: following therapy response through liquid biopsy in metastatic colorectal cancer patients

Conditions: Metastatic Colorectal Cancer

Summary: detection of progressive disease by neuropeptide y (npy) methylation in liquid biopsies in patients with ras and braf wild-type, unresectable, metastatic colorectal cancer receiving first-line treatment folfox/folfiri and panitumumab.

prospective, multicentric interventional study to optimize the cutoff value of npy methylation in liquid biopsies in metastatic colorectal cancer patients treated with first-line folfox/folfiri and panitumumab. inclusion is possible after histologically or cytologically proven colorectal adenocarcinoma with metastatic lesions according to recist 1.1 at the start of first-line treatment using folfox/folfiri and panitumumab. patient must have a proven ras and braf wild-type tumor. patients will be followed by study protocol up to and including the first ct scan following the last liquid biopsies taken, or when a follow-up period of 11 months is reached, until death, until metastasectomy, until lost to follow-up or until (consent) withdrawal.

Eligibility criteria:
inclusion criteria: * man or woman ≥ 18 years of age at the time the informed consent is obtained * eastern cooperative oncology group (ecog) performance status of 0 or 1 * histologically or cytologically confirmed adenocarcinoma of the colon or rectum in subjects with unresectable metastatic (m1) disease * at least 1 uni-dimensionally measurable lesion of at least 10 mm per recist 1.1 guidelines using conventional techniques (ct scan). lesion must not be chosen from a previously irradiated field, unless there has been documented disease progression in that field after irradiation and prior to inclusion. all sites of disease must be evaluated \<28 days prior to the start of first-line therapy * wild-type ras tumor status (of tumor tissue) * wild-type braf tumor status (of tumor tissue) * adequate hematologic, renal, hepatic and coagulation function * starting a first-line treatment with a combination of folfox/folfiri and panitumumab exclusion criteria: * history of prior or concurrent central nervous system metastases * history of other malignancy, except: * malignancy treated with curative intent and with no known active disease present for ≥ 3 years prior to start therapy and felt to be at low risk for recurrence by the treating physician * adequately treated non-melanomatous skin cancer or lentigo maligna without evidence of disease * adequately treated cervical carcinoma in situ without evidence of disease * prostatic intraepithelial neoplasia without evidence of prostate cancer * prior chemotherapy or other systemic anticancer therapy for the treatment of metastatic colorectal carcinoma including but not limited to bevacizumab and anti-epidermal growth factor receptor (egfr) therapy (e.g. cetuximab, panitumumab, erlotinib, gefitinib, lapatinib) * prior adjuvant chemotherapy (including oxaliplatin therapy) or other adjuvant systemic anticancer therapy including but not limited to bevacizumab and anti-egfr therapy (e.g. cetuximab, panitumumab, erlotinib, gefitinib, lapatinib) for the treatment of colorectal cancer ≤ 6 months prior to start therapy with the following exceptions: * subjects may have received prior fluoropyrimidine therapy if administered solely for the purpose of radiosensitization for the adjuvant or neoadjuvant treatment of rectal cancer * radiotherapy ≤ 14 days prior to start therapy. subjects must have recovered from all radiotherapy-related toxicities. * significant cardiovascular risk * history of interstitial lung disease (e.g., pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on diagnostic ct scan * active inflammatory bowel disease or other bowel disease causing chronic diarrhea (defined as ≥ common terminology criteria (ctc) grade 2, \[common terminology criteria for adverse events (ctcae) version 5.0\]) * peripheral sensory neuropathy (≥ ctc grade 2 \[ctcae version 5.0\])